Brain Tumor Vaccine Shows Promise in Early Trials

MONDAY April 11, 2011 -- A vaccine that jumpstarts the immune system is showing promise in keeping a deadly type of cancerous brain tumor at bay.

Glioblastoma, or malignant glioma, is the most common type of cancerous brain tumor. It's also deadly -- most people die about 12 to 14 months after diagnosis, said Dr. Isaac Yang, a neurosurgeon at University of California, Los Angeles, and lead author of a study on the vaccine.

Sen. Ted Kennedy died from a glioblastoma in 2009.

In the clinical trials, researchers created individualized vaccines for 34 patients using brain tumor tissue and the patient's own dendritic cells, which are part of the immune system.

When joined together in a vaccine, introducing the tumor cells to the dendritic cells "trains" the immune system to recognize cancer cells and mount an attack, the researchers said.

About 91 percent of patients who received the vaccine were alive after one year. Fifty-five percent were alive after two years, while 44 percent survived to three years or longer.

Three patients are still alive after five years, Yang said.

"What we're trying to do is to train the immune system like a hunting dog," Yang said. "A hunting dog is given something to sniff. What the vaccine does is give the immune system the right 'scent' so that it recognizes the brain cancer and goes and kills it."

The results of the Phase 1 clinical trial were to be reported Monday at the American Association of Neurological Surgeons annual meeting in Denver.

The researchers are currently wrapping up Phase 2 clinical trials. The next step is a Phase 3, multi-center trial, which is currently enrolling patients, Yang said.

There's growing interest in using individualized vaccines to treat certain cancers, said William Chambers, director of clinical cancer research and immunology for the American Cancer Society. Last year, the U.S. Food and Drug Administration approved a vaccine to treat prostate cancer that also works by stimulating the immune system.

Chambers said the results of the brain tumor trials look "promising. The increase in months of survival is pretty striking."

Still, not everyone with a glioblastoma tumor would be a candidate for the vaccine, he said, including people whose cancer is so deep in their brain or so advanced that it's inoperable. That includes nearly half of all patients, Chambers noted.

And being able to operate isn't the only challenge with this type of brain tumor. Glioblastoma tumors send out tentacles that infiltrate the surrounding areas of the brain, Chambers said.

Neurosurgeons use microscopes to guide them during surgery, Yang said. Yet even when they seem to have removed all of the tumor, it inevitably comes back.

What the vaccine seems to do is to help the immune system battle those spreading glioblastoma cells after the visible tumor is removed.

In the trials, researchers tested two types of vaccines. One, called "whole tumor dendritic cell lysate," was created using tissue from the whole tumor to mount a broad immune system attack, Yang said. The other vaccine was specifically designed to seek out and attack specific peptides, or markers, on the tumor cells.

The "whole tumor" vaccine worked better, Yang said. The average survival for those patients was about 36 months (three years) compared to about 18 months for those who received the marker-specific vaccine.

Because this study was presented at a medical meeting, the data and conclusions should be viewed as preliminary until published in a peer-reviewed journal.

Another measure of the success of cancer treatments is "time to progression," or how long it took for the tumor to come back. Within both vaccine groups, this varied widely -- anywhere between a few months and several years -- and there was no statistically significant difference between the two groups.

It's possible that even when the tumor comes back sooner rather than later, the vaccine may still prolong survival because the tumor grows more slowly than it would without the immune system boost, Yang said.

In the study, patients received the vaccine every two weeks at first, and then a booster every three months after that.

And despite the promising results, a vaccine is unlikely to ever cure brain tumors, Yang said.

Tumors are constantly changing, and over time produce molecules that turn off or interfere with immune responses, Chambers said.

Still, researchers hope that cancer vaccines will eventually be able to keep tumors at bay for many years and "convert glioblastoma from a fatal disease into a chronic disease," Yang said.

"This is individualized medicine," Yang said. "Each person's vaccine is different because each person's brain cancer is different. We've been treating every brain cancer as if they are the same, but they're not."

More information

The U.S. National Cancer Institute has more on brain tumors.

Posted: April 2011


View comments

Hide
(web4)